CREMα belongs to a superfamily of transcription factors that also includes other CREM homologs, such as inducible cAMP early repressor (ICER), cAMP responsive element binding proteins (CREB)-1 and -2, and the CREM/activating transcription factors (ATF)-1, -2, and -3 (Figure 1). All members share high sequence homology within their DNA binding domains (a basic leucine zipper domain) and bind to the common palindromic consensus element 5′-TGACGTCA-3′, the cAMP responsive element (CRE), or its 5′-half-site [16]. The name ‘CRE’ originates from the observation that CREB and CREM proteins are activated upon an increase of intracellular cAMP levels. The CREM/ CREB signaling cascade comprises various extracellular signals including growth factors or hormones that bind to transmembrane receptors which, in turn, drive adenylate cyclase to generate high levels of cAMP. Cyclic AMP can then promote the enzymatic properties of protein kinases, such as PKA, PKC, and casein kinases I and II that can phosphorylate and thereby activate CREB/CREM proteins [17]. Serine residue 117 of CREM is one target for activating protein kinases [18]. In the context of T cell biology, T cell receptor (TCR)
